Pembrolizumab single dose half-life following 2 mg/kg, 10 mg/kg, and 200 mg was 15.1, 15.8, and 12.3 days, respectively. Serum exposure at the doses studied (range, 2-10 mg/kg) was approximately linear; steady-state area under the curve0-21 days (95% confidence interval [CI]) was 730.9 (627.4-851.6), 2,819.2 (2,009.4-3,955.4), and 931.0 (724.4-1,196.6) μg•day/mL, respectively. After 7.9 (range, 0.7-13.1) months median follow-up overall, objective response rate was 14.3% (95% CI, 5.4%-28.5%); median progression-free survival was 2.1 (95% CI, 2.1-4.2) months, and median overall survival was not reached (95% CI, 6.6 months-not reached). CONCLUSION Pembrolizumab had manageable toxicity, linear serum exposure, and encouraging antitumor activity in Chinese patients with advanced NSCLC. © AlphaMed Press; the data published online to support this summary are the property of the authors.PURPOSE In the late1990s, reacting to the outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom that caused a new variant of Creutzfeldt-Jakob disease (vCJD) in humans, manufacturers withdrew bovine heparin from the market in the United States. There have been growing concerns about the adequate supply and safety of porcine heparin. Since the BSE epidemic has been declining markedly, the US Food and Drug Administration reevaluates the vCJD risk via use of bovine heparin. METHODS We developed a computational model to estimate the vCJD risk to patients receiving bovine heparin injections.  https://www.selleckchem.com/products/talabostat.html  The model incorporated information including BSE prevalence, infectivity levels in the intestines, manufacturing batch size, yield of heparin, reduction in infectivity by manufacturing process, and the dose-response relationship. RESULTS The model estimates a median risk of vCJD infection from a single intravenous dose (10 000 USP units) of heparin made from US-sourced bovine intestines to be 6.9 × 10-9 (2.5-97.fifth percentile 1.5 × 10-9 -4.3 × 10-8 ), a risk of 1 in 145 million, and 4.6 × 10-8 (2.5-97.fifth percentile 1.1 × 10-8 -2.6 × 10-7 ), a risk of 1 in 22 million for Canada-sourced products. The model estimates a median risk of 1.4 × 10-7 (2.5-97.fifth percentile 2.9 × 10-8 -9.3 × 10-7 ) and 9.6 × 10-7 (2.5-97.fifth percentile 2.1 × 10-7 -5.6 × 10-6 ) for a typical treatment for venous thromboembolism (infusion of 2-4 doses daily per week) using US-sourced and Canada-sourced bovine heparin, respectively. CONCLUSIONS The model estimates the vCJD risk from use of heparin when appropriately manufactured from US or Canadian cattle is likely small. The model and conclusions should not be applied to other medicinal products manufactured using bovine-derived materials. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.OBJECTIVE This study aimed to describe the genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions (PHT-induced cADRs) in Thai patients. METHOD A retrospective case-control study was conducted among 88 PHT- cADRs (25 SJS/TEN, 37 DRESS/DIHS and 26 MPE) compared to 70 PHT-tolerant controls during 2008-2017. Genotyping was performed by Taqman RT-PCR (EPHX1 337 T > C, EPHX1 416A > G and CYP2C9*3), pyrosequencing (UGT1A1*28, UGT1A1*6) and polymerase chain reaction-sequence-specific oligonucleotide probe (HLA-B). Chi-squared test and binary logistic regression were used to identify factors associated with PHT-cADRs. RESULTS Multivariate analysis showed that HLA-B*4601 was significantly associated with all PHT-induced cADRs (OR 2.341; 95% CI, 1.078-5.084; P = .032). Age of ≥60 years showed a significant association with PHT-induced SJS/TEN (OR 3.600; 95% CI, 1.214-10.672; P = .021). CYP2C9*3 was almost reaching statistically associated with an increased risk of PHT-induced SJS/TEN (OR 4.800; 95% CI, 0.960-23.990; P = .056). While HLA-B*5602/04 was found to have a significant association with PHT-induced DRESS/DIHS (OR 29.312; 95% CI, 1.213-707.994; P = .038). Moreover, female gender and HLA-B*4001 were associated with an increased risk of PHT-induced MPE at OR 5.734; 95% CI, 0.910-58.351; P = .042 and OR 3.647; 95% CI, 1.193-11.147; P = .023, respectively. CONCLUSION Both clinical (advanced age, female gender) and genetic factors (HLA-B*4601, CYP2C9*3, HLA-B*5602/04 and HLA-B*4001) contributed to the risk of PHT-induced cADRs. Further studies with larger sample size may be warranted to confirm these findings and also the influence of EPHX1 gene. © 2020 John Wiley & Sons Ltd.OBJECTIVE To determine the rate and risk factors for osteoradionecrosis (ORN) in osseous free flaps after postoperative radiation therapy (PORT). To describe the treatment of free flap ORN. METHODS Seventy-four patients undergoing osseous free flap reconstruction were analyzed. Thirty-eight completed PORT. Patients were followed for ≥6 months. RESULTS The rate of ORN was 34% overall; 0% with 50 to 59.9 Gy; 8% with 60 Gy; 40% with 66 Gy; 56% with 70 to 74.4 Gy. Mean time to ORN was 13.1 months. 0/28 patients without PORT developed free flap osteonecrosis. Multivariate analysis found the only factor predicting ORN PORT >60 Gy, which increased the risk 21-fold. Treatment included PENTACLO, hyperbaric oxygen, and surgical debridement with 75% within 2 years. CONCLUSION PORT >60 Gy is significantly associated with free flap ORN. As the dose of adjuvant RT increases beyond 60 Gy, the risk of ORN in free flaps rises. Consideration should be given to lower PORT doses or delaying free flap reconstruction when feasible. © 2020 Wiley Periodicals, Inc.Two-dimensional (2D) undoped layered perovskite oxynitride materials have been suggested as potential visible-light-responsive photocatalysts; however, there have been few investigations on their use as photocatalysts because of the difficulty in synthesis and stability issues when in contact with water. Here, we demonstrate the synthesis of a new layered perovskite oxynitride, K2LaTa2O6N, as an exceptional example of a water-tolerant photocatalyst for H2 evolution under visible light. K2LaTa2O6N, prepared from KLaTa2O7 and K2CO3 as precursors, underwent in situ H+/K+ exchange in aqueous solution while keeping its visible light absorption capability. Thus protonated K2LaTa2O6N, K2-xHxLaTa2O6N, modified with an Ir cocatalyst, exhibited excellent catalytic activity toward H2 evolution in the presence of I- as an electron donor and under visible light irradiation; the activity was 6 times higher than Pt/ZrO2/TaON, one of the best-performing oxynitride photocatalysts for H2 evolution. Overall water splitting was also achieved using the Ir-loaded, protonated K2LaTa2O6N in combination with Cs-modified Pt/WO3 as an O2 evolution photocatalyst in the presence of I3-/I- shuttle redox couple.